1. Loss of Keap1 contributes to LSCC pathogenesis by activating the NRF2–ROS pathway.
Loss of Keap1 contributes to LSCC pathogenesis by activating the NRF2–ROS pathway. A,In vitro cell proliferation of K/P-LSCC and P-LSCC cells (N = 3). B,In vivo tumor growth of K/P-LSCC and P-LSCC tumors (N = 8). C,In vitro cell invasion of K/P-LSCC and P-LSCC cells (N = 3). D,In vivo lung metastasis of K/P-LSCC and P-LSCC cells (N = 6). Microscopic metastatic foci in the lung were counted. E, Enrichment plots for highly enriched gene sets from GSEA of RNA-seq data (Supplementary Fig. S5A). Gene sets related to stem cells, ROS biology, NF-κB, and Notch are shown. F and G, FACS analysis (F) and bar graph (G) of intracellular ROS levels of K/P-LSCC and P-LSCC cells. ROS levels were measured by DCFDA staining. H, Expression of NF-κB target genes in K/P-LSCC and P-LSCC cells assayed by qRT-PCR (N = 3). I, Expression of NRF2 target genes in K/P-LSCC and P-LSCC cells (N = 3). J,In vitro cell proliferation of K/P-LSCC and P-LSCC cells transduced with control or shNrf2 lentivirus (N = 3). K,In vivo growth of K/P-LSCC and P-LSCC tumors with and without shNrf2 lentivirus transduction (N = 6). L, expression of Notch1 target genes in K/P-LSCC and P-LSCC cells (N = 3). All data from A–D and G–L are presented as mean ± SEM (*, P < 0.05; **, P < 0.01; ***, P < 0.001).
Youngtae Jeong et al. Cancer Discov 2017;7:86-101
©2017 by American Association for Cancer Research